RESUMO
Magnet-mediated gene therapy has gained considerable interest from researchers as a novel alternative for treating genetic disorders, particularly through the use of superparamagnetic iron oxide nanoparticles (NPs)-such as magnetite NPs (Fe3O4NPs)-as non-viral genetic vectors. Despite their commercial availability for specific genetic transfection, such as in microglia cell lines, many potential uses remain unexplored. Still, ethical concerns surrounding the use of human DNA often impede genetic research. Hence, this study examined DNA-coated Fe3O4NPs (DNA-Fe3O4NPs) as potential transfection vectors for human foreskin fibroblasts (HFFs) and A549 (lung cancer) cell lines, using banana (Musa sp.) as a low-cost, and bioethically unproblematic DNA source. Following coprecipitation synthesis, DNA-Fe3O4NP characterization revealed a ζ-potential of 40.65 ± 4.10 mV, indicating good colloidal stability in aqueous media, as well as a superparamagnetic regime, evidenced by the absence of hysteresis in their magnetization curves. Successful DNA coating on the NPs was confirmed through infrared spectra and surface analysis results, while magnetite content was verified via characteristic X-ray diffraction peaks. Transmission electron microscopy (TEM) determined the average size of the DNA-Fe3O4NPs to be 14.69 ± 5.22 nm. TEM micrographs also showed no morphological changes in the DNA-Fe3O4NPs over a 30-day period. Confocal microscopy of HFF and A549 lung cancer cell lines incubated with fluoresceinamine-labeled DNA-Fe3O4NPs demonstrated their internalization into both the cytoplasm and nucleus. Neither uncoated Fe3O4NPs nor DNA-Fe3O4NPs showed cytotoxicity to A549 lung cancer cells at 1-50 µg/mL and 25-100 µg/mL, respectively, after 24 h. HFFs also maintained viability at 1-10 µg/mL for both NP types. In conclusion, DNA-Fe3O4NPs were successfully internalized into cells and exhibited no cytotoxicity in both healthy and cancerous cells across a range of concentrations. These NPs, capable of binding to various types of DNA and RNA, hold promise for applications in gene therapy.
Assuntos
DNA , Nanopartículas de Magnetita , Musa , Humanos , Nanopartículas de Magnetita/química , Musa/química , Células A549 , Frutas/química , Fibroblastos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Transfecção , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular TumoralRESUMO
The search for new strategies to curb the spread of the SARS-CoV-2 coronavirus, which causes COVID-19, has become a global priority. Various nanomaterials have been proposed as ideal candidates to inactivate the virus; however, because of the high level of biosecurity required for their use, alternative models should be determined. This study aimed to compare the effects of two types of nanomaterials gold (AuNPs) and silver nanoparticles (AgNPs), recognized for their antiviral activity and affinity with the coronavirus spike protein using PhiX174 and enveloped Phi6 bacteriophages as models. To reduce the toxicity of nanoparticles, a species known for its intermediate antiviral activity,Solanum mammosumL. (Sm), was used. NPs prepared with sodium borohydride (NaBH4) functioned as the control. Antiviral activity against PhiX174 and Phi6 was analyzed using its seed, fruit, leaves, and essential oil; the leaves were the most effective on Phi6. Using the aqueous extract of the leaves, AuNPs-Sm of 5.34 ± 2.25 nm and AgNPs-Sm of 15.92 ± 8.03 nm, measured by transmission electron microscopy, were obtained. When comparing NPs with precursors, both gold(III) acetate and silver nitrate were more toxic than their respective NPs (99.99% at 1 mg ml-1). The AuNPs-Sm were less toxic, reaching 99.30% viral inactivation at 1 mg ml-1, unlike the AgNPs-Sm, which reached 99.94% at 0.01 mg ml-1. In addition, cell toxicity was tested in human adenocarcinoma alveolar basal epithelial cells (A549) and human foreskin fibroblasts. Gallic acid was the main component identified in the leaf extract using high performance liquid chromatography with diode array detection (HPLC-DAD). The FT-IR spectra showed the presence of a large proportion of polyphenolic compounds, and the antioxidant analysis confirmed the antiradical activity. The control NPs showed less antiviral activity than the AuNPs-Sm and AgNPs-Sm, which was statistically significant; this demonstrates that both theS. mammosumextract and its corresponding NPs have a greater antiviral effect on the surrogate Phi bacteriophage, which is an appropriate model for studying SARS-CoV-2.
Assuntos
COVID-19 , Nanopartículas Metálicas , Solanum , Humanos , Nanopartículas Metálicas/química , Ouro/farmacologia , Ouro/química , SARS-CoV-2 , Espectroscopia de Infravermelho com Transformada de Fourier , Prata/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
Assuntos
COVID-19 , Nanopartículas Metálicas , COVID-19/terapia , Humanos , Nanopartículas Metálicas/uso terapêutico , Pandemias , SARS-CoV-2/efeitos dos fármacos , PrataRESUMO
ABSTRACT The global COVID-19 pandemic initiated in Ecuador with the patient zero in February 2020 and since more than 40,000 persons have been tested positive to the virus, leaving some 3,500 deceased, while approximately about 10,500 persons above annual average numbers died within March to May. A strict lockdown was applied by mid-March, which resulted to a severe economic crisis in the country. Although during the lockdown occurred a notable decrease in the number of new cases, the spread of the infection was already massive, untechnical, political and economic decisions will certainly lead to continuous wave of infections for months. Objective Our study postulates, that persons who are most likely to be infected during such secondary wave will be people who have already health issues to which we count besides the known ones, especially those who are already suffer by the distribution of volcanic ashes, as such pyroclastic material is known to affect lunges and thyroids. Methods A descriptive ecological study of information related to COVID-19 infection at a national level using official data from the Minister of Public Health and volcanic ash fall by geographical area in Ecuador. Results The mortality rate per canton indicated that those with lower attack rates are the ones with highest mortality rate. For instance, Portovelo (21.3/100,000), Playas (18.4/100,000), Santa Rosa (15.8/100,000), Suscal (15.3/100,000) and Penipe (14.3/100,000) reported the highest mortality rate per 100,000 people. The main distribution of such volcanic material is within the central to northern area of the Highlands and Inter-Andean Valley of Ecuador, due to the analysis of some 7394 satellite images of the last 21 years. Conclusions We conclude that areas with high vulnerabilities are also most susceptible to develop COVID-19. Such areas with their respective populations will be affected above average and shall be protected in particular within the presently starting during possible second wave of infection.(AU)
RESUMEN La pandemia de COVID-19 inició en Ecuador en febrero de 2020. Desde el inicio más de 40 000 personas han sido oficialmente diagnosticadas con el virus, que ha dejado al menos 3 500 fallecidas, mientras que aproximadamente unas 10 500 personas por encima del promedio anual murieron entre marzo y mayo de 2020. A mediados de marzo se aplicó el confinamiento absoluto en el país, lo que provocó una grave crisis económica y social en Ecuador. Aunque el bloqueo produjo una reducción en el número de casos, la infección estaba propagada ya entre la comunidad y los diagnósticos aumentaron notable debido a decisiones políticas y económicas, que, sin lugar a duda, conducirán a oleadas posteriores de infección por incluso meses. Objetivo Nuestro estudio postula que las personas que tienen más probabilidades de infectarse durante dicha ola secundaria serán las personas que ya tengan problemas de salud. A la vez, proponemos que aquellos pobladores que ya están sufriendo por la caída de cenizas volcánicas y flujos piroclásticos pueden tener más riesgo tal como lo describimos en casos relacionados con cáncer de tiroides y ceniza. Métodos Es un estudio ecológico descriptivo de la información relacionada con la infección por COVID-19 a nivel nacional, utilizando datos oficiales de contagio del Ministerio de Salud Pública y caída de cenizas volcánicas por área geográfica en Ecuador. Resultados La tasa de mortalidad por cantón indicó que aquellos con tasas de ataque más bajas son los que tienen la tasa de mortalidad más alta. Por ejemplo, Portovelo (21,3 / 100.000), Playas (18,4 / 100.000), Santa Rosa (15,8 / 100 000), Suscal (15,3 / 100 000) y Penipe (14,3 / 100 000) registraron la tasa de mortalidad más alta por cada 100 000 personas. La principal distribución de dicho material volcánico se encuentra dentro de la zona centro-norte de la Sierra y Valle Interandino del Ecuador, debido al análisis de unas 7 394 imágenes satelitales de los últimos 21 años. Conclusiones Concluimos que las áreas con alta vulnerabilidad también son más susceptibles a desarrollar COVID-19. Tales áreas con sus respectivas poblaciones se verán afectadas por encima de la media y estarán protegidas, en particular, dentro del inicio actual durante una posible segunda ola de infección.(AU)